Tapping the potential of mRNA in cellular reprogramming and beyond

Eterna Therapeutics CEO on harnessing the potential of mRNA engineering in cellular reprogramming, gene therapy and longevity.

At the recent annual meeting of the American Society of Gene and Cell Therapy, one company stood out for the sheer number of presentations it delivered. mRNA cell engineering company Eterna Therapeutics gave no fewer than eight presentations, with subjects ranging from gene editing and insertion in human cells to lipid nanoparticle delivery systems.

At the same event, the company also revealed what it says is potentially the first multi-cell-type therapeutic strategy derived from induced pluripotent stem cells, which mimics how the human immune system naturally fights disease.

Longevity.Technology: In recent years, Eterna has been busy assembling a vast array of gene editing and cell reprogramming technologies, in-licensing and acquiring IP from companies including Factor Bioscience and Exacis Biotherapeutics. The company has already engaged in collaborations on longevity applications of its technologies, such as the treatment of central nervous system disorders and other neurology indications. To learn more about the company’s strategy, we caught up with CEO Dr Matt Angel.

Angel joined Eterna last year from Factor Bioscience, a company he founded to explore the potential of mRNA technology.

Tapping the potential of mRNA in cellular reprogramming and beyond // Eterna Therapeutics interview
Dr Matt Angel is the CEO of Eterna Therapeutics

“We’ve seen the amazing things that mRNA can do in the vaccine space, but I think this is really just the tip of the iceberg,” he says. “Over the course of the last 12 years, Factor conducted research into mRNA with a focus on cell engineering. It built up a patent portfolio of more than 130 granted patents in the areas of mRNA, gene editing, and cell reprogramming, which is now exclusively licensed to Eterna. All of this is of particular interest in the field of longevity and aging research, which has been a personal passion of mine from day one.”

A multi-therapy approach

Factor created gene-editing technologies that enable the deletion, insertion, and repair of DNA sequences in living cells. It also developed cell-reprogramming technologies that enable the generation of clonal lines of pluripotent stem cells, which can be expanded and differentiated into a desired cell type for the development of regenerative cell therapies.

“Eterna has now in-licensed all of the technology that Factor developed in this mRNA cell engineering space – the entire patent portfolio,” says Angel. “We are well positioned to harness the potential to develop new therapeutic candidates based on these technologies.”

Eterna aims to do this by directly addressing the causes of disease, using mRNA to express gene editing proteins, for example, to repair mutations that may be causing disease. It also intends to use cell reprogramming therapeutically – using mRNA to express proteins in cells that cause them to de-differentiate, essentially turning them back into a pluripotent stem cell state, indistinguishable from embryonic stem cells.

“Cell reprogramming is an area of research that has been very active over the last decade or so,” says Angel. “But much of the work in the field of pluripotent stem cell research has relied on viral approaches or DNA-based approaches that we believe have some challenges when it comes to clinical translation and ultimately developing viable therapeutics that are actually going to help people. Eterna’s approach would not rely on those technologies, but instead be able to leverage proprietary non-viral, non-DNA based approaches, using mRNA.”

Turning back the cellular clock

Angel is excited about the potential of cellular reprogramming to “turn back the clock” at a cellular level.  

“In preclinical studies, we’ve shown re-expression of telomerase reverse transcriptase and extension of telomeres inside cells,” he says. “And so, in addition to turning an adult cell back into an embryonic like cell, we’re effectively rejuvenating the cell at every level, making it younger.”

For Eterna, the initial objective of its reprogramming technology is to create tissue-specific cells for specific therapeutic applications. The company recently announced its first out-licensing partnership with cell therapy company Lineage Cell Therapeutics.

“That partnership is focused on neurology indications, central nervous system indications, using our rejuvenated reprogrammed cells to generate new cells for patients with neurological diseases,” says Angel. “The intention is that as we progress through the development of these kinds of therapies, not only would we be potentially replacing missing or damaged cells in these patients, but by replacing them with rejuvenated cells, we’re going to potentially see more far-reaching impacts of these kinds of therapies. And I think it may start opening the doors to research into very interesting applications focused on aging and longevity.”

The power of mRNA in cellular reprogramming

Engineering mRNA is such a powerful tool because of its versatility – with just the right change of the sequence, it is possible for mRNA to have markedly different characteristics. As such, Eterna’s initial focus is on engineering mRNA to effectively express proteins, or combination of proteins in its cell engineering portfolio.

“For example, one of the areas of our portfolio relates to direct expression using mRNA of telomerase reverse transcriptase itself,” he explains. “The intention here is that we’re directly extending the replicative potential of cells and lengthening the time before the onset of senescence, by extending their telomeres directly using a purely mRNA-based approach.”

“In some ways, it’s the most straightforward way of thinking about cellular rejuvenation or reprogramming – using a direct expression of proteins. Between that at one end of the spectrum and complete reprogramming to pluripotency at the other, there are many different steps that one can take by directly expressing different proteins to achieve different phenotypic changes in cells. It all comes down to the specific application.”

Ready for therapeutic development

With such an extensive portfolio of IP and technology, with such broad applications, how does Eterna plan to proceed?

“We find ourselves sitting on top of a mountain of technology on which we have an excellent foundation to build our programs,” says Angel. “And strategic collaborations and partnerships are a very viable option to realizing the full potential of these technologies.”

In addition to its recent collaboration with Lineage Cell Therapeutics, Eterna also recently announced the acquisition of the immuno-oncology platform of Exacis Biotherapeutics.

“Lineage is a great example of how we can deploy the technology to generate therapeutic products in collaboration with other companies,” says Angel. “And with the Exacis platform, we believe that we are in a great position to take the next step in the immuno-oncology area of medicine to generate additional data and potentially advanced candidates in that area.”

“We’ve been hammering away at unlocking the potential of mRNA for cell engineering applications over the last decade, and we have finally reached the point where we’re ready to advance beyond the lab bench and into potential therapeutic candidate development.”